T cel targeting in Sjogren syndroom

Reducing immunopathology in patients with primary Sjogren syndrome by selective effector T cell targeting

Onderzoeksstage: 6/9 maanden
Scriptie mogelijk: nee

Patients with primary Sjogren syndrome (pSS) suffer from chronic stimulation of the immune system. Several immunomodulatory therapies had very limited effects on inflammation and clinical symptoms, indicating a need for better therapies. There is evidence to suggest that IL-7Rα+ effector T cells play an important role in inflammation and tissue destruction in pSS. Selective targeting of this aggressive T cell population could be a novel treatment strategy for pSS. However, before such a therapy becomes a realistic approach the following questions need to be answered:
1) In what way do IL-7R ligands IL-7 and thymic stromal lymphopoeitin (TSLP) activate effector T cells, B cells and dendritic cells?
2) How do effector T cells and suppressive T cells influence proinflammatory and tissue-destructive activity of B cells, macrophages and glandular tissue cells of Sjögren patients?
3) Can specific targeting of effector T cells prevent inflammation and tissue destruction?

Techniques
Culture of human tissue and/or cells; MACS cell sorting to isolate T cells (and subsets) B cells and monocytes; cell phenotyping by FACS analysis; intra-cellular cytokine staining; cytokine assessment by ELISA; proliferation assays; immunohistochemistry.

Contactpersonen:
Dr. Joel van Roon
J.vanRoon@umcutrecht.nl, 088-755 7063

Prof. Floris Lafeber
F.Lafeber@umcutrecht.nl, 088-755 8521

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